MCID: SPN251
MIFTS: 27

Spondyloenchondrodysplasia with Immune Dysregulation

Categories: Genetic diseases, Immune diseases

Aliases & Classifications for Spondyloenchondrodysplasia with Immune Dysregulation

MalaCards integrated aliases for Spondyloenchondrodysplasia with Immune Dysregulation:

Name: Spondyloenchondrodysplasia with Immune Dysregulation 57 25 75 37 29 13 6 73
Combined Immunodeficiency with Autoimmunity and Spondylometaphyseal Dysplasia 57 25 75
Spencdi 57 25 75
Roifman Immunoskeletal Syndrome 57 75
Spencd 57 75
Spondyloenchondrodysplasia, with Immune Dysregulation 40
Spondyloenchondrodysplasia 73
Roifman-Melamed Syndrome 25
Roifman-Costa Syndrome 25

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset, from infancy to 15 years
marked clinical variability, both within and between families
variable severity, from infantile death due to autoimmune thrombocytopenia to isolated skeletal dysplasia in adult patient


HPO:

32
spondyloenchondrodysplasia with immune dysregulation:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spondyloenchondrodysplasia with Immune Dysregulation

OMIM : 57 Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an immunoosseous dysplasia combining the typical metaphyseal and vertebral bone lesions of spondyloenchondrodysplasia (SPENCD) with immune dysfunction and neurologic involvement. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present (Menger et al., 1989). Central nervous system involvement includes spasticity, mental retardation, and cerebral calcifications, and immune dysregulation ranges from autoimmunity to immunodeficiency. Neurologic and autoimmune manifestations have been observed in different combinations within a single family, suggesting that this disorder may be defined by specific radiographic features but has remarkably pleiotropic manifestations (Renella et al., 2006). Briggs et al. (2016) also noted variability in skeletal, neurologic, and immune phenotypes, which was sometimes marked between members of the same family. (607944)

MalaCards based summary : Spondyloenchondrodysplasia with Immune Dysregulation, also known as combined immunodeficiency with autoimmunity and spondylometaphyseal dysplasia, is related to spondyloenchondrodysplasia, and has symptoms including muscle spasticity An important gene associated with Spondyloenchondrodysplasia with Immune Dysregulation is ACP5 (Acid Phosphatase 5, Tartrate Resistant). Affiliated tissues include bone, t cells and skin, and related phenotypes are low-set ears and recurrent otitis media

Genetics Home Reference : 25 Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an inherited condition that primarily affects bone growth and immune system function. The signs and symptoms of SPENCDI can become apparent anytime from infancy to adolescence.

UniProtKB/Swiss-Prot : 75 Spondyloenchondrodysplasia with immune dysregulation: A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone.

Related Diseases for Spondyloenchondrodysplasia with Immune Dysregulation

Diseases related to Spondyloenchondrodysplasia with Immune Dysregulation via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 spondyloenchondrodysplasia 28.4 ACP5 ZNF627

Symptoms & Phenotypes for Spondyloenchondrodysplasia with Immune Dysregulation

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
otitis media, multiple episodes

Growth Height:
short stature

Hematology:
thrombocytopenia
idiopathic thrombocytopenic purpura (itp)

Respiratory Lung:
pneumonia
restrictive lung disease
interstitial fibrosis

Skin Nails Hair Skin:
hyperpigmented macules
hypopigmented skin patches on arms (vitiligo)

Respiratory:
recurrent respiratory tract infections (upper and lower)

Skin Nails Hair Hair:
normal hair shaft morphology

Neurologic Central Nervous System:
spasticity
spastic diplegia
cns calcifications, esp. basal ganglia, on ct scan
progressive spastic quadriparesis
mild mental retardation (in some patients)

Skeletal Spine:
platyspondyly
kyphoscoliosis
irregular vertebral endplates
increased lumbar lordosis
posterior vertebral body radiolucencies

Immunology:
lymphadenopathy
combined humoral and cellular immunodeficiency
recurrent infections (pneumonia, sinusitis, fulminant varicella)
autoimmune disorders (i.e., itp, juvenile rheumatoid arthritis (jra), hypothyroidism, crohn disease)
decreased t cell response to mitogens
more
Skeletal:
spondylometaphyseal dysplasia

Head And Neck Nose:
narrow, pointy nose

Skeletal Limbs:
symmetric radiolucencies in long bone metaphyses
sclerotic, irregular metaphyses (distal radii and ulnae, distal femurs, proximal fibulae)

Endocrine Features:
hypothyroidism (autoimmune)


Clinical features from OMIM:

607944

Human phenotypes related to Spondyloenchondrodysplasia with Immune Dysregulation:

32 (show all 31)
# Description HPO Frequency HPO Source Accession
1 low-set ears 32 HP:0000369
2 recurrent otitis media 32 HP:0000403
3 narrow nose 32 HP:0000460
4 hypothyroidism 32 HP:0000821
5 platyspondyly 32 HP:0000926
6 purpura 32 HP:0000979
7 hypermelanotic macule 32 HP:0001034
8 vitiligo 32 HP:0001045
9 intellectual disability, mild 32 occasional (7.5%) HP:0001256
10 spastic diplegia 32 HP:0001264
11 rheumatoid arthritis 32 HP:0001370
12 autoimmune thrombocytopenia 32 HP:0001973
13 pneumonia 32 HP:0002090
14 restrictive ventilatory defect 32 HP:0002091
15 recurrent respiratory infections 32 HP:0002205
16 progressive spastic quadriplegia 32 HP:0002478
17 spondylometaphyseal dysplasia 32 HP:0002657
18 lymphadenopathy 32 HP:0002716
19 kyphoscoliosis 32 HP:0002751
20 lumbar hyperlordosis 32 HP:0002938
21 immune dysregulation 32 HP:0002958
22 metaphyseal irregularity 32 HP:0003025
23 irregular vertebral endplates 32 HP:0003301
24 short stature 32 HP:0004322
25 metaphyseal sclerosis 32 HP:0004979
26 cellular immunodeficiency 32 HP:0005374
27 combined immunodeficiency 32 HP:0005387
28 decrease in t cell count 32 HP:0005403
29 tubulointerstitial fibrosis 32 HP:0005576
30 hypopigmented skin patches on arms 32 HP:0007526
31 recurrent sinusitis 32 HP:0011108

UMLS symptoms related to Spondyloenchondrodysplasia with Immune Dysregulation:


muscle spasticity

Drugs & Therapeutics for Spondyloenchondrodysplasia with Immune Dysregulation

Search Clinical Trials , NIH Clinical Center for Spondyloenchondrodysplasia with Immune Dysregulation

Genetic Tests for Spondyloenchondrodysplasia with Immune Dysregulation

Genetic tests related to Spondyloenchondrodysplasia with Immune Dysregulation:

# Genetic test Affiliating Genes
1 Spondyloenchondrodysplasia with Immune Dysregulation 29 ACP5

Anatomical Context for Spondyloenchondrodysplasia with Immune Dysregulation

MalaCards organs/tissues related to Spondyloenchondrodysplasia with Immune Dysregulation:

41
Bone, T Cells, Skin, Lung

Publications for Spondyloenchondrodysplasia with Immune Dysregulation

Articles related to Spondyloenchondrodysplasia with Immune Dysregulation:

# Title Authors Year
1
A new case of spondyloenchondrodysplasia with immune dysregulation confirms the pleiotropic nature of the disorder: comment on "A syndrome of immunodeficiency, autoimmunity, and spondylometaphyseal dysplasia" by M.L. Kulkarni, K. Baskar, and P.M. Kulkarni [2006]. ( 17497723 )
2007

Variations for Spondyloenchondrodysplasia with Immune Dysregulation

UniProtKB/Swiss-Prot genetic disease variations for Spondyloenchondrodysplasia with Immune Dysregulation:

75
# Symbol AA change Variation ID SNP ID
1 ACP5 p.Lys52Met VAR_065920
2 ACP5 p.Thr89Ile VAR_065921 rs387906668
3 ACP5 p.Gly109Arg VAR_065922 rs781050795
4 ACP5 p.Leu201Pro VAR_065923 rs387906672
5 ACP5 p.Gly215Arg VAR_065924 rs781199182
6 ACP5 p.Asp241Asn VAR_065925
7 ACP5 p.Asn262His VAR_065926
8 ACP5 p.Met264Lys VAR_065927 rs387906670

ClinVar genetic disease variations for Spondyloenchondrodysplasia with Immune Dysregulation:

6
(show all 42)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACP5 NM_001111035.2(ACP5): c.266C> T (p.Thr89Ile) single nucleotide variant Pathogenic rs387906668 GRCh37 Chromosome 19, 11687654: 11687654
2 ACP5 NM_001111035.2(ACP5): c.266C> T (p.Thr89Ile) single nucleotide variant Pathogenic rs387906668 GRCh38 Chromosome 19, 11576839: 11576839
3 ACP5 NM_001111035.2(ACP5): c.667C> T (p.Gln223Ter) single nucleotide variant Pathogenic rs387906669 GRCh37 Chromosome 19, 11687126: 11687126
4 ACP5 NM_001111035.2(ACP5): c.667C> T (p.Gln223Ter) single nucleotide variant Pathogenic rs387906669 GRCh38 Chromosome 19, 11576311: 11576311
5 ACP5 NM_001111035.2(ACP5): c.791T> A (p.Met264Lys) single nucleotide variant Pathogenic rs387906670 GRCh37 Chromosome 19, 11686012: 11686012
6 ACP5 NM_001111035.2(ACP5): c.791T> A (p.Met264Lys) single nucleotide variant Pathogenic rs387906670 GRCh38 Chromosome 19, 11575197: 11575197
7 ACP5 NM_001111035.2(ACP5): c.643G> C (p.Gly215Arg) single nucleotide variant Pathogenic rs781199182 GRCh38 Chromosome 19, 11576335: 11576335
8 ACP5 NM_001111035.2(ACP5): c.643G> C (p.Gly215Arg) single nucleotide variant Pathogenic rs781199182 GRCh37 Chromosome 19, 11687150: 11687150
9 ACP5 NM_001111035.2(ACP5): c.325G> A (p.Gly109Arg) single nucleotide variant Pathogenic rs781050795 GRCh37 Chromosome 19, 11687595: 11687595
10 ACP5 NM_001111035.2(ACP5): c.325G> A (p.Gly109Arg) single nucleotide variant Pathogenic rs781050795 GRCh38 Chromosome 19, 11576780: 11576780
11 ACP5 NM_001111035.2(ACP5): c.831_833delCTA (p.Tyr278del) deletion Pathogenic rs387906671 GRCh37 Chromosome 19, 11685970: 11685972
12 ACP5 NM_001111035.2(ACP5): c.831_833delCTA (p.Tyr278del) deletion Pathogenic rs387906671 GRCh38 Chromosome 19, 11575155: 11575157
13 ACP5 NM_001111035.2(ACP5): c.602T> C (p.Leu201Pro) single nucleotide variant Pathogenic rs387906672 GRCh37 Chromosome 19, 11687191: 11687191
14 ACP5 NM_001111035.2(ACP5): c.602T> C (p.Leu201Pro) single nucleotide variant Pathogenic rs387906672 GRCh38 Chromosome 19, 11576376: 11576376
15 ACP5 NM_001111035.2(ACP5): c.814C> T (p.Arg272Cys) single nucleotide variant Benign/Likely benign rs147025508 GRCh37 Chromosome 19, 11685989: 11685989
16 ACP5 NM_001111035.2(ACP5): c.814C> T (p.Arg272Cys) single nucleotide variant Benign/Likely benign rs147025508 GRCh38 Chromosome 19, 11575174: 11575174
17 ACP5 NM_001611.4(ACP5): c.131C> T (p.Thr44Met) single nucleotide variant Pathogenic rs369804864 GRCh38 Chromosome 19, 11577187: 11577187
18 ACP5 NM_001611.4(ACP5): c.131C> T (p.Thr44Met) single nucleotide variant Pathogenic rs369804864 GRCh37 Chromosome 19, 11688002: 11688002
19 ACP5 NM_001611.4(ACP5): c.816dupC (p.Lys273Glnfs) duplication Pathogenic rs879255600 GRCh37 Chromosome 19, 11685987: 11685987
20 ACP5 NM_001611.4(ACP5): c.816dupC (p.Lys273Glnfs) duplication Pathogenic rs879255600 GRCh38 Chromosome 19, 11575172: 11575172
21 ACP5 NM_001111035.2(ACP5): c.772_790del19 (p.Ser258Trpfs) deletion Pathogenic rs878853218 GRCh38 Chromosome 19, 11575198: 11575216
22 ACP5 NM_001111035.2(ACP5): c.772_790del19 (p.Ser258Trpfs) deletion Pathogenic rs878853218 GRCh37 Chromosome 19, 11686013: 11686031
23 ACP5 NM_001111035.2(ACP5): c.661G> A (p.Val221Ile) single nucleotide variant Benign rs2229532 GRCh38 Chromosome 19, 11576317: 11576317
24 ACP5 NM_001111035.2(ACP5): c.661G> A (p.Val221Ile) single nucleotide variant Benign rs2229532 GRCh37 Chromosome 19, 11687132: 11687132
25 ACP5 NM_001111035.2(ACP5): c.245A> G (p.Asn82Ser) single nucleotide variant Uncertain significance rs202233676 GRCh38 Chromosome 19, 11577073: 11577073
26 ACP5 NM_001111035.2(ACP5): c.245A> G (p.Asn82Ser) single nucleotide variant Uncertain significance rs202233676 GRCh37 Chromosome 19, 11687888: 11687888
27 ACP5 NM_001111035.2(ACP5): c.855T> C (p.Thr285=) single nucleotide variant Benign rs77911902 GRCh37 Chromosome 19, 11685948: 11685948
28 ACP5 NM_001111035.2(ACP5): c.855T> C (p.Thr285=) single nucleotide variant Benign rs77911902 GRCh38 Chromosome 19, 11575133: 11575133
29 ACP5 NM_001111035.2(ACP5): c.693C> T (p.Tyr231=) single nucleotide variant Benign rs373030121 GRCh37 Chromosome 19, 11687100: 11687100
30 ACP5 NM_001111035.2(ACP5): c.693C> T (p.Tyr231=) single nucleotide variant Benign rs373030121 GRCh38 Chromosome 19, 11576285: 11576285
31 ACP5 NM_001111035.2(ACP5): c.386G> A (p.Arg129His) single nucleotide variant Uncertain significance rs199580546 GRCh37 Chromosome 19, 11687534: 11687534
32 ACP5 NM_001111035.2(ACP5): c.386G> A (p.Arg129His) single nucleotide variant Uncertain significance rs199580546 GRCh38 Chromosome 19, 11576719: 11576719
33 ACP5 NM_001111035.2(ACP5): c.276C> T (p.Asp92=) single nucleotide variant Benign rs34375794 GRCh38 Chromosome 19, 11576829: 11576829
34 ACP5 NM_001111035.2(ACP5): c.276C> T (p.Asp92=) single nucleotide variant Benign rs34375794 GRCh37 Chromosome 19, 11687644: 11687644
35 ACP5 NM_001111035.2(ACP5): c.137G> A (p.Arg46Gln) single nucleotide variant Uncertain significance rs201184983 GRCh38 Chromosome 19, 11577181: 11577181
36 ACP5 NM_001111035.2(ACP5): c.137G> A (p.Arg46Gln) single nucleotide variant Uncertain significance rs201184983 GRCh37 Chromosome 19, 11687996: 11687996
37 ACP5 NM_001111035.2(ACP5): c.738C> A (p.Tyr246Ter) single nucleotide variant Pathogenic rs761798208 GRCh37 Chromosome 19, 11686065: 11686065
38 ACP5 NM_001111035.2(ACP5): c.738C> A (p.Tyr246Ter) single nucleotide variant Pathogenic rs761798208 GRCh38 Chromosome 19, 11575250: 11575250
39 ACP5 NM_001111035.2(ACP5): c.601C> T (p.Leu201=) single nucleotide variant Benign rs568957938 GRCh37 Chromosome 19, 11687192: 11687192
40 ACP5 NM_001111035.2(ACP5): c.601C> T (p.Leu201=) single nucleotide variant Benign rs568957938 GRCh38 Chromosome 19, 11576377: 11576377
41 ACP5 NM_001111035.2(ACP5): c.861C> T (p.Asp287=) single nucleotide variant Benign rs147115345 GRCh37 Chromosome 19, 11685942: 11685942
42 ACP5 NM_001111035.2(ACP5): c.861C> T (p.Asp287=) single nucleotide variant Benign rs147115345 GRCh38 Chromosome 19, 11575127: 11575127

Expression for Spondyloenchondrodysplasia with Immune Dysregulation

Search GEO for disease gene expression data for Spondyloenchondrodysplasia with Immune Dysregulation.

Pathways for Spondyloenchondrodysplasia with Immune Dysregulation

GO Terms for Spondyloenchondrodysplasia with Immune Dysregulation

Sources for Spondyloenchondrodysplasia with Immune Dysregulation

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